Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Oxid Med Cell Longev. 2017;2017:9396425. doi: 10.1155/2017/9396425. Epub 2017 Oct 22.
Paraquat (PQ) is one of the most used herbicide worldwide. Its cytotoxicity is attributed to reactive radical generation. Resveratrol (Res) and montelukast (MK) have anti-inflammatory and antioxidant properties. The protective effects of Res, MK, or their combination against PQ-induced acute liver injury have not been investigated before. Therefore, we explored the protective potential of Res and/or MK against PQ hepatic toxicity in a mouse model. Mice were randomly assigned to five groups: group I served as the normal control and group II received a single dose of PQ (50 mg/kg, i.p.). Groups III, IV, and V received PQ plus oral Res (5 mg/kg/day), MK (10 mg/kg/day), and Res/MK combination, respectively. Res and/or MK reduced PQ-induced liver injury, evidenced by normalization of serum total protein, ALT, and AST. Res and/or MK significantly reversed PQ-induced oxidative stress markers glutathione and malondialdehyde. Res and/or MK significantly reduced PQ-induced inflammation reflected in TNF- levels. Furthermore, Res and/or MK reversed PQ-induced apoptosis assessed by differential expression of , , and . Histopathologic examination supported the biochemical findings. Although Res and MK displayed antioxidative, anti-inflammatory, and antiapoptotic activities, their combination was not always synergistic.
百草枯（PQ）是世界上使用最广泛的除草剂之一。其细胞毒性归因于活性自由基的产生。白藜芦醇（Res）和孟鲁司特（MK）具有抗炎和抗氧化作用。Res、MK 或它们的组合对 PQ 诱导的急性肝损伤的保护作用以前尚未被研究过。因此，我们在小鼠模型中探索了 Res 和/或 MK 对 PQ 肝毒性的保护潜力。小鼠被随机分为五组：第 I 组作为正常对照组，第 II 组接受单次 PQ（50mg/kg，ip）注射。第 III、IV 和 V 组分别接受 PQ 加口服 Res（5mg/kg/天）、MK（10mg/kg/天）和 Res/MK 联合治疗。Res 和/或 MK 降低了 PQ 诱导的肝损伤，表现为血清总蛋白、ALT 和 AST 的正常化。Res 和/或 MK 显著逆转了 PQ 诱导的氧化应激标志物谷胱甘肽和丙二醛。Res 和/或 MK 显著降低了 PQ 诱导的 TNF-α 水平所反映的炎症。此外，Res 和/或 MK 通过差异表达 、 和 逆转了 PQ 诱导的细胞凋亡。组织病理学检查支持生化发现。尽管 Res 和 MK 表现出抗氧化、抗炎和抗凋亡活性，但它们的组合并不总是协同的。
